Transient adrenocortical insufficiency of prematurity and systemic hypotension in very low birthweight infants

Abstract

Objectives: A proportion of preterm, very low birthweight (VLBW, < 1500 g) infants may show inadequate adrenal response to stress in the immediate postnatal period. The human corticotrophin releasing hormone (hCRH) stimulation test was used to: (a) determine the relation between pituitary-adrenal response and systemic blood pressure in these infants; (b) characterise the endocrinological features of transient adrenocortical insufficiency of prematurity (TAP).

Study design: A total of 226 hCRH tests were performed on 137 VLBW infants on day 7 and 14 of life in a tertiary neonatal centre.

Results: Basal, peak, and incremental rise in serum cortisol (Delta Cort(0-30)) on day 7 were associated significantly with the lowest systolic, mean, and diastolic blood pressures recorded during the first two weeks of life (r > 0.25, p < 0.005). These cortisol concentrations also correlated significantly but negatively with the maximum and total cumulative dose of dopamine (r > -0.22, p < 0.02), dobutamine (r > -0.18, p < 0.04), and adrenaline (r > -0.26, p < 0.004), total volume of crystalloid (r > -0.22, p < 0.02), and duration of inotrope treatment (r > -0.25, p < 0.006). Multivariate regression analysis of significant factors showed that the lowest systolic, mean, and diastolic blood pressures remained independently associated with serum cortisol (basal, peak, and Delta Cort(0-30)) on day 7. Hypotensive infants requiring inotropes (group 2) were significantly less mature and more sick than infants with normal blood pressure (group 1). The areas under the ACTH response curves were significantly greater in group 2 than in group 1, on both day 7 (p = 0.004) and day 14 (p = 0.004). In contrast, the area under the cortisol response curve was significantly greater in group 1 than in group 2 on day 7 (p = 0.001), but there was no significant difference between the two groups on day 14. In addition, serum cortisol at the 50th centile in hypotensive infants had high specificity and positive predictive value (0.80-0.93 and 0.81-0.89 respectively) for predicting early neonatal hypotension.

Conclusions: This study characterises the fundamental endocrinological features of TAP: normal or exaggerated pituitary response; adrenocortical insufficiency; good recovery of adrenal function by day 14 of postnatal life. The results also provide the centiles of serum cortisol for hypotensive patients and infants with normal blood pressure, and show a significant relation between serum cortisol and blood pressure in VLBW infants.

Figure 1

Patient recruitment process of the study. NEC, Necrotising enterocolitis.

Figure 2

Adrenocorticotrophin (ACTH) response of the human corticotrophin releasing hormone test on days 7 and 14 in very low birthweight infants with relatively normal blood pressure (group 1) and in hypotensive infants requiring inotropic support (group 2). The values are mean (SEM). The area under the curve (AUC) is significantly greater in group 2 than in group 1, on both day 7 (p = 0.004) and 14 (p = 0.004).

Figure 3

Cortisol response of the human corticotrophin releasing hormone test on day 7 and 14 in very low birthweight infants with relatively normal blood pressure (group 1) and in hypotensive infants requiring inotropic support (group 2). The values are mean (SEM). The area under the curve (AUC) is significantly greater in group 1 than in group 2 on day 7 (p = 0.001).